Ultrasensitivity of Cell Adhesion to the Presence of Mechanically Strong Ligands

Abstract

Integrins, a class of membrane proteins involved in cell adhesion, participate in the cell’s sensing of the mechanical environments. We previously showed that, for the initial cell adhesion to occur, single integrins need to experience a threshold force of 40 pico-Newton (pN) through their bond with surface-bound ligands. This force requirement was determined using a series of double-stranded DNA tethers called tension gauge tethers (TGTs), each with a different rupture force, linked to the ligand. Here, we performed cell-adhesion experiments using surfaces coated with two different TGTs, one of a strong rupture force (around 54 pN) and the other of a weak rupture force (around 12 pN). When presented with one type of TGT only, cells adhered to the strong TGT-coated surface but not to the weak TGT-coated surface. However, when presented with both, the presence of the strong TGTs transforms the way cells respond to the weak TGTs such that cells treat both TGTs the same, as if the weak TGTs were strong. Furthermore, a subpopulation of cells can adhere to and spread on a surface displaying just a few molecules of the strong TGTs per cell if, and only if, they are presented along with many weak TGTs. This ultrasensitivity to just a few tethers that can withstand strong forces raises a question of how the cells can achieve such remarkable sensitivity to their mechanical environment without amplifying noise.